Abstract—The study was aimed at investigating the peculiarities of the conformational changes in serum albumin in patients with anxious and melancholic depression. Albumin conformation was measured by the method of the subnanosecond laser time resolved fluorescence spectroscopy. Anxious depression was accompanied by a significant decrease in the values of the three amplitudes of the serum albumin in comparison with controls. In the melancholic depression, the values of all three amplitudes of serum albumin molecules were significantly elevated in comparison with controls. These results clearly indicate that anxious and melancholic depression are accompanied by oppositely directed changes in serum albumin conformation.

The aim of the study was investigation of the peculiarities of the conformational changes of serum albumin in patients with anxious and melancholic depression. Albumin conformation was measured by the method of the subnanosecond laser time resolved fluorescence spectroscopy. Anxious depression was followed with the significant decrease of the values of the three amplitudes on the serum albumin in comparison with controls. In the melancholic depression the values of all three amplitudes on serum albumin molecules were significantly elevated in comparison with controls. These results are clearly indicated that anxious and melancholic depression are followed by differently directed changes in serum albumin conformation.

Introduction.Approaches to therapy, predicting the dynamics and evaluating the effectiveness of psychopharmacotherapy of mood disorders is an extremely important problem in biological psychiatry.The fluorescence of a tryptophan residue is very sensitive to changes in the structure of its environment in the protein.In human serum albumin (HSA), radiation at wavelengths from 295 to 305 nm absorbs mainly tryptophan (Trp214), which, as an internal probe of albumin molecules, makes it possible to selectively observe the state of the albumin molecule and its possible conformational changes.Objective: to study the kinetics of fluorescence decay of HSA tryptophan in patients with melancholic depression using subnanosecond fluorescence spectroscopy.Material.We examined 14 patients (the main group) diagnosed with ICD-10 melancholic depression (MD), their psychopathological state was assessed as a depressive episode within the framework of bipolar affective disorder (F31.3) or recurrent depressive disorder (F33.1).The control group consisted of 14 volunteers without morbid changes according to the results of express diagnostics of clinical-psychopathological and clinical-biochemical studies.There were no statistically significant differences between the examined groups in terms of age and sex parameters.Methods.Psychometric quantification of the severity of depressive symptoms was assessed using the Hamilton Depression Rating Scale (HAMD-21, HDRS-21) and Anxiety Rating Scale (HARS).The examination was carried out on the first day of the patient's admission to the hospital before the start of active psychopharmacological treatment.Tryptophan fluorescence decay kinetics were measured on a Laser Emission Diode setup with a pulsed light source.The excitation wavelength was 290±10 nm.Results.Analysis of all parameters of tryptophan fluorescence decay in blood serum samples of the examined groups before the start of therapy showed that the average values of the A1 and A3 amplitudes in the serum of patients with MD of the main group were statistically significantly (p=0.01)lower than in the control group of volunteers (for A1 -378 versus 440, for A3 -285 versus 327, respectively).Conclusion.Based on the results of the study, it was demonstrated that conformational changes in the albumin molecule in patients with mental pathology (melancholic depression) can be detected using subnanosecond fluorescence spectroscopy of fluorescent tryptophan residua, which confirms the scientific novelty, practical significance of the work and the need to continue this direction.

The aim of the study was to investigate the serum albumin conformation in patients with melancholic depression. There were investigated 22 patients with melancholic depression and 54 healthy volunteers. Patients with melancholic depression were investigated in dynamics of the antidepressive therapy (venlafaxine, 75–150 mg/daily): at admission, on 15th and 30 th days. Subnanosecond laser time resolved fluorescence spectroscopy with K-35 fluorescent probe (dimethylaminonaphthalic acid N-carboxyphenylimide, CAPIDAN) was used for the investigation of albumin conformation There were revealed in controls 3 binding site for the probe on albumin molecule with decay times of 1, 3 and 9 nanoseconds (amplitudes A 3 , A 2 , and A 1 , respectively). The mean amplitudes A 3 , A 2 , and A 1 in the serum albumin of patients with melancholic depression were significantly higher than in controls ( p = 0.025). After antidepressive therapy with venlafaxine there was revealed that all three amplitudes significantly decreased and were equal to the amplitudes of controls. We can hypothesize that investigated parameters can serve as potential biomarkers for the evaluation of the efficacy of the psychopharmacotherapy.

Abstract—The kinetics of fluorescence decay of the K-35 probe and the tryptophan amino acid residue were measured after the addition of sodium hypochlorite in human albumin serum (HSA). The K-35 fluorescent probe (excitation 405 nm, fluorescence 530 nm) binds to drug binding site I of albumin. During the experiment the molar concentration of albumin in the fraction varied from 0.3 to 20 μM. Oxidation of the fraction with hypochlorite was recorded by the change in the fluorescence of tryptophan also located in binding site I of albumin (excitation 290 nm, fluorescence 350 nm). It was shown that, at serum albumin concentration of about 30 μM, HSA has antioxidant activity which maintains its ability to bind ligands even after exposure to relatively large amounts of hypochlorite (up to 50 oxidizing molecules per protein molecule). HSA retains its ability to bind ligands because the properties of the K-35 probe during oxidation remained almost unchanged and we observed only insignificant changes in binding characteristics. The added hypochlorite is, predominantly, used to oxidize albumin amino acids, including Trp oxidation as observed in the experiment. For 14 sera of donors, we showed significant differences in the fluorescence of oxidized and native tryptophan.

We consider social learning where agents can only observe part of the population (modeled as neighbors on an undirected graph), face many decision problems, and arrival order of the agents is unknown. The central question we pose is whether there is a natural observability graph that prevents the information cascade phenomenon. We introduce the ‘celebrities graph’ and prove that indeed it allows for proper information aggregation in large populations even when the order at which agents decide is random and even when different issues are decided in different orders.

Abstract—The goal of this work was to search for blood serum parameters that would be associated with the state of patients with mental disorders. Such indicators are needed for an objective assessment of this state versus the prevailing subjective evaluation methodologies. The kinetics of tryptophan fluorescence decay in the serum albumin fraction was compared in patients with melancholic depression (before treatment) and in healthy volunteers. Albumin fluorescence is mainly due to the tryptophan 214 residue, which is located in the immediate vicinity of the first drug-binding center of the molecule. The decay kinetics were described as a sum of three exponential functions with lifetimes τi (in the 6.5, 2.8 and 1.0 ns region) and the amplitudes Ai. The τi values were similar in both groups of individuals. In contrast, there was a significant difference between patients and controls in the A1/A3 amplitude ratio. It is suggested that the A1/A3 value can be considered as a potential marker indicating the presence or absence of melancholic depression in patients before treatment.

In this paper, the state of the body’s antioxidant defense was studied using the state of thiol groups in the albumin in patients with their first episode of schizophrenia (FES). We examined 21 patients with the first psychotic attack of schizophrenia; the average severity of the disorders was 75 ± 2 points on the PANSS scale. All patients were examined prior to initiation of the drug therapy. The control group consisted of ten healthy volunteers. The concentration and reactivity of the albumin SH groups was determined in the reaction with dithionitrobenzoic acid. As a result of the study, we found a 24% decrease in the average reactivity of albumin SH groups in the FES group compared with the control group (p = 0.02). Using two parameters, that is, the concentration and reactivity of albumin thiols, it was possible to separate the patient group and the control group, with the probability of a relationship of the patient to the respective group of 86%. Thus, patients with the first episode of schizophrenia before the start of treatment are characterized by significant disturbances in the concentration and reactivity of the albumin SH-groups involved in redox processes in the body.

BACKGROUND:Risperidone is an antipsychotic drug. In blood, this drug binds mainly to human serum albumin (HSA) and is also transported by HSA.METHOD:To study certain details of the interaction between risperidone and HSA, a fluorescent dye CAPIDAN was used as a reporter. This dye specifically fluoresces from HSA in serum and is highly sensitive to structural changes in HSA including pathology-induced changes. Interaction of CAPIDAN with HSA has been studied using time-resolved fluorescence techniques.RESULT:The addition of phenylbutazone, a marker for the HSA drug-binding site I, leads to displacement of CAPIDAN from this site due to direct competition between phenylbutazone and the dye. The addition of risperidone induces a response of CAPIDAN fluorescence that is highly similar to its response to phenylbutazone. This response depends strongly on ionic strength and is very similar in both cases, phenylbutazone and risperidone. This similarity suggests that risperidone binds to HSA in the region of site I. In this site, the risperidone molecule probably covers the positive charge of Arginine 218 or Arginine 222 preventing their interaction with the CAPIDAN negatively charged carboxyl group. This effect was observed both in isolated HSA and in serum, suggesting similarity of the interaction.CONCLUSION:Thus, risperidone is able to prevent binding of organic anions (i.e. CAPIDAN as a drug-like molecule) to HSA.

ObjectivesDiscovery of biomarkers for evaluation of efficacy of psychopharmacotherapy is important task.AimTo study parameters characteristic for albumin binding sited in melancholic depression (MD) using fluorescent laser spectroscopy in range of 30–50 picoseconds.Methods22 patients with MD (dep) (F33.1 and 2) were investigated in dynamics of antidepressant therapy (venlafaxine: 75–150 mg/daily) for 30 days. Control group (con) consists of 54 volunteers. Decay of fluorescence amplitude (A) of fluorescent probe K-35 from serum albumin was measured using laser. Earlier, we revealed 3 binding sites in albumin with amplitudes A1, A2 and A3 with decay time of 1, 3 and 9 nanoseconds, respectively.ResultsThere was revealed significant decrease of amplitude A1dep, normalized on mean value of A1 for controls (A1dep/A1con), for patients with MD after treatment with venlafaxine. In this case, A1depvalues decreased and were equal to A1 values of controls (P < 0.01): A1dep/A1con before treatment–1.23 and after 30 days of therapy–0.97 relative units; for controls this value was–1.00 relative units. The same type of normalization was observed for amplitudes A2 and A3 of melancholic patients. There were revealed significant changes of A3/A1 ratio that points out on conformational changes of serum albumin molecule in dynamics of venlafaxine therapy.ConclusionWe have registered unidirectional changes in albumin molecule in patients with MD. Investigated parameters can serve as potential biomarkers for evaluation of efficacy of psychopharmacotherapy.Disclosure of interestThe authors have not supplied their declaration of competing interest.

It is known that the conformation of human serum albumin binding sites is sensitive to pathological processes. In this work, changes in the physical–chemical properties of albumin binding sites in melancholic depression were studied. The K-35 fluorescent probe (dimethylaminonaphthalic acid N-carboxyphenylimide, CAPIDAN) was used as a reporter of these changes. It is shown that the fluorescence decay of K-35 depends on the state of the drug-binding sites of albumin. The kinetics of fluorescence decay were measured with a time resolution of approximately 30–50 ps. The parameters that characterize the fluorescence decay of K-35 in serum were reliably responsive to melancholic depression and the dynamics of its treatment. With melancholic depression, a decrease in the concentration of nonesterified long-chain fatty acids that are capable of affecting binding sites of serum albumin was observed. However, variations in the concentration of NEFA cannot be considered as a cause of the alterations of albumin binding sites. In addition to NEFA, other factors are likely to affect structural and physical-chemical properties of albumin in depression patients.

OBJECTIVE:Conformational protein changes may be an important component of the disturbance of molecular processes in the development of pathological process in the body. We studied conformations of albumin molecule in the blood of patients with depression using biophysical -nanotechnical approach.MATERIAL AND METHODS:We examined 19 patients with depression and 25 healthy controls. Properties of serum albumin were compared in patients with typical melancholic depression and controls using spectroscopy (subnanosecond range) with K-35 fluorescent probe.RESULTS AND CONCLUSION:The properties of albumin binding sites in patients before and after treatment differed from those in controls. The authors suggest that it points to the changes in albumin molecule conformation that may influence the functional state of the protein. It has been suggested that these changes may be considered as biomarkers of pharmacotherapeutic efficacy.

While past neuroimaging methods have contributed greatly to our understanding of brain function after traumatic brain injury (TBI), resting state functional MRI (rsfMRI) connectivity methods have more recently provided a far more unbiased approach with which to monitor brain circuitry compared to task-based approaches. However, current knowledge on the physiologic underpinnings of the correlated blood oxygen level dependent signal, and how changes in functional connectivity relate to reorganizational processes that occur following injury is limited. The degree and extent of this relationship remain to be determined in order that rsfMRI methods can be fully adapted for determining the optimal timing and type of rehabilitative interventions that can be used post-TBI to achieve the best outcome. Very few rsfMRI studies exist after experimental TBI and therefore we chose to acquire rsfMRI data before and at 7, 14 and 28 days after experimental TBI using a well-known, clinically-relevant, unilateral controlled cortical impact injury (CCI) adult rat model of TBI. This model was chosen since it has widespread axonal injury, a well-defined time-course of reorganization including spine, dendrite, axonal and cortical map changes, as well as spontaneous recovery of sensorimotor function by 28 d post-injury from which to interpret alterations in functional connectivity. Data were co-registered to a parcellated rat template to generate adjacency matrices for network analysis by graph theory. Making no assumptions about direction of change, we used two-tailed statistical analysis over multiple brain regions in a data-driven approach to access global and regional changes in network topology in order to assess brain connectivity in an unbiased way. Our main hypothesis was that deficits in functional connectivity would become apparent in regions known to be structurally altered or deficient in axonal connectivity in this model. The data show the loss of functional connectivity predicted by the structural deficits, not only within the primary sensorimotor injury site and pericontused regions, but the normally connected homotopic cortex, as well as subcortical regions, all of which persisted chronically. Especially novel in this study is the unanticipated finding of widespread increases in connection strength that dwarf both the degree and extent of the functional disconnections, and which persist chronically in some sensorimotor and subcortically connected regions. Exploratory global network analysis showed changes in network parameters indicative of possible acutely increased random connectivity and temporary reductions in modularity that were matched by local increases in connectedness and increased efficiency among more weakly connected regions. The global network parameters: shortest path-length, clustering coefficient and modularity that were most affected by trauma also scaled with the severity of injury, so that the corresponding regional measures were correlated to the injury severity most notably at 7 and 14 days and especially within, but not limited to, the contralateral cortex. These changes in functional network parameters are discussed in relation to the known time-course of physiologic and anatomic data that underlie structural and functional reorganization in this experiment model of TBI.